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Biomedical subjects

M Lesser

Publications and source records attributed to M Lesser.

At least 55 records · Page 3Linked to original sources
PubMed1987

Proteolytic activity in sheep lung lymph as marker of lung capillary injury.

Intravenous infusions of Escherichia coli endotoxin into sheep caused the appearance in lung lymph of high levels of an enzyme with trypsinlike activity. The time course of appearance of the enzyme and the extent of its increase corresponded to the known events of endotoxin-induced capillary injury. Accordingly, activity was low in the first phase of endotoxin-induced increased lung lymph flow caused by increased pressure filtration but was high in the second phase of increased lung lymph flow caused by increased permeability filtration. Recovery was associated with a decrease of activity to preinfusion levels. Capillary damage and increased permeability filtration induced by air emboli or oleic acid led to a similar increase in lung lymph proteolytic activity. By contrast lung lymph proteolytic activity remained virtually unchanged during increased pressure filtration induced by inflation of a balloon in the left atrium. Activity also remained unchanged in thoracic duct lymph, indicating that the increased activity in lung lymph is not an expression of a generalized response to endotoxin. The enzyme, a serine protease with a molecular weight of about 70,000 to 75,000 and a pH optimum between 7.3 and 7.6, was not related to lymph clotting and was not capable of correcting the clotting defects of plasmas deficient in enzymes of the clotting cascade. These results together with specificity studies indicate that the enzyme represents a new, hitherto unidentified, protease. Measurements of its activity in lung lymph represent a sensitive marker of lung capillary injury.

Animals↗
PubMed1986

Are prognostic factors for local control of breast cancer treated by primary radiotherapy significant for patients treated by mastectomy?

Recent follow-up studies of patients with mammary carcinoma treated with breast-conserving primary radiotherapy identified a triad of pathologic features significantly associated with local treatment failure. These unfavorable characteristics of the primary tumor were: poor or undifferentiated nuclear grade; intraductal carcinoma within the tumor mass; and intraductal carcinoma in breast tissue outside the perimeter of the primary lesion. The current study was undertaken to assess the impact of these same factors on the prognosis of 573 consecutively treated women, with invasive duct carcinomas 5 cm or less in diameter, and who underwent mastectomy. Histologic sections of all primary tumors were reviewed, and the lesions were classified according to the distribution of intraductal carcinoma present: only within the tumor (IN, 247 cases, 43%), only outside the tumor (OUT, 25 cases, 4%), within the outside (IN-OUT, 158 cases, 28%), or not seen (IFDC, 143 cases, 25%). The median follow-up period for the entire series was 56 months. Ninety-five (17%) patients were dead of disease (median time to death, 36 months). Variables that proved to be statistically significant for overall survival were nodal status (P less than 0.001), nuclear grade (P less than 0.03), and histologic grade (P less than 0.007). Nodal status (P less than 0.001), histologic grade (P less than 0.001), and tumor size (P = 0.01) were significant predictors of disease-free survival. The pattern of intraductal carcinoma, when present, was not predictive of the risk for recurrence or survival in women treated by mastectomy. These findings provide a rationale for additional surgical treatment for women whose tumors have features more likely to be associated with local failure following primary radiotherapy. To permit more detailed pathologic examination of the primary lesion, the initial excision should be carried out separately from the treatment when limited resection and radiation are to be considered as a treatment option.

Breast Neoplasms↗
PubMed1986

Increased cathepsin B-like activity in alveolar macrophages and bronchoalveolar lavage fluid from smokers.

Cathepsin B-like activity was determined in alveolar macrophages (AM) and cell-free bronchoalveolar lavage fluid (BALF) obtained from volunteers who were current cigarette smokers and compared with that found in lifetime nonsmokers. Enzyme activity was determined with benzyloxycarbonyl-Leu-Leu-Arg-2-naphthylamide as the substrate. Specific activity of the enzyme was more than twice as high in AM from smokers than in cells from nonsmokers (35,600 +/- 2,250 versus 16,000 +/- 860; p less than 0.001) and about 10 times as high in BALF from smokers than in that from nonsmokers (3,060 +/- 380 versus 300 +/- 25; p less than 0.001). Because cathepsin B is capable of degrading structural lung proteins and inactivating alpha-1-proteinase inhibitor, and the elastinolytic activity of AM may be mediated through cysteine proteinases such as cathepsin B, the finding of high concentrations of an enzyme with cathepsin B-like activity in AM and BALF from smokers suggests the need to explore the role of the enzyme in structural lung damage associated with cigarette smoking.

Adult↗
PubMed1986

Long-term evolution of BCG- and CFA-induced granulomas in rat lungs. Correlation of histologic features with cells in bronchoalveolar lavage samples.

Granulomatous inflammation was induced in the lungs of rats for assessment of the suitability of this animal species for long-term study of granuloma development and resolution and for comparison of the histologic changes with the cellular profile in bronchoalveolar lavage (BAL) samples. It was found that after a single intravenous injection of bacillus Calmette-Guérin (BCG) organisms suspended in saline-0.01% Triton, complete Freund's adjuvant (CFA), or BCG suspended in CFA (BCG + CFA), distinct pathologic patterns developed in the lungs during the acute stages. BCG alone caused numerous small epithelioid granulomas associated with interstitial infiltration; CFA alone caused large discrete granulomas with minimal interstitial changes, and BCG + CFA caused large granulomas associated with diffuse interstitial infiltration. Following CFA or BCG + CFA the maximum number and size of granulomas were reached approximately 4 weeks after injection. By 8 weeks collagen was seen in the larger granulomas in sections stained with hematoxylin and eosin from animals given CFA or BCG + CFA. Maximum collagen deposition was seen at 16 weeks. From that point onward the degree of collagen deposition decreased, so that by approximately 42 weeks collagen was no longer seen. At 52 weeks residual granulomatous lesions consisted of a few foci of foamy macrophages surrounded by several layers of lymphocytes or epithelioid cells surrounded by dense layers of lymphocytes. Bronchoalveolar lavage samples revealed that at all time periods the number of leukocytes was increased and that the increase was due primarily to an influx of macrophages and lymphocytes. The increase in number of lymphocytes was so striking that at the peak of granulomatous changes following injection of BCG + CFA up to 50% of the total cells were found to be lymphocytes. The total number of leukocytes in BAL samples and the absolute number of lymphocytes closely paralleled the intensity of histologic changes seen in microscopic sections. It is concluded that the intravenous injection of BCG, CFA, or BCG + CFA in rats causes distinct and profound granulomatous patterns that are associated with increased cellularity in BAL samples. The findings suggest that the rat may be an excellent model for study of the mechanisms of granuloma development and resolution.

Animals↗
PubMed1985

Cathepsin B and D activity in stimulated peritoneal macrophages.

Highly sensitive and specific synthetic substrates were used to quantitate cathepsin B and D activity in peritoneal macrophages in response to stimulation in vivo with mineral oil and thioglycollate. After intraperitoneal instillation of mineral oil the activity of cathepsin B increased significantly (to 15 300 units/mg protein versus 7 340 in saline controls), reaching values approaching those found in alveolar macrophages (18 400 units/mg protein). Significantly greater stimulation of enzyme activity was obtained after intraperitoneal instillation of thioglycollate (23 600 units/mg protein). Cathepsin D activity also increased significantly after both mineral oil and thioglycollate. However, the increase was moderate (from 806 to about 1 200 units/mg protein), remaining still more than six times lower than in alveolar macrophages. The data are the first to demonstrate that cathepsin B activity can be stimulated in vivo in peritoneal macrophages by instillation of agents that induce acute inflammation. They also point to a differential control of expression of cathepsin B and D activity in both peritoneal and alveolar macrophages in spite of the common lysosomal origin of the two enzymes.

Animals↗
PubMed1985

A comparison of flow gradients across disposable arterial perfusion cannulas.

Five-hundred members of The Society of Thoracic Surgeons were canvassed to discover which cannulas are currently used for open-heart surgical procedures in adults; 120 surgeons responded. The mean arterial line pressure produced by 29 disposable arterial perfusion cannulas (size range, 16F to 30F) at flow rates of 1 to 5 liters per minute was compared. A roller pump with perfusion tubing 95 mm (0.75 inch) in diameter was used with water as the test solution. Line pressures in these cannulas ranged from 22.4 +/- 2.30 (standard deviation) to 271.0 +/- 6.60 mm Hg at 5 L/min. Four 24F cannulas had gradients of less than 55 mm Hg at a flow rate of 5 L/min, and 6 cannulas--4 of which were 22F and 2, 24F--had gradients higher than 150 mm Hg at 5 L/min. A number of cannulas kinked easily, and these showed marked increases in line pressure. The following results were obtained from this study: (1) a wide range of line pressures was observed in disposable arterial perfusion cannulas currently in clinical use; (2) some cannulas currently used for cardiopulmonary bypass in adults generated excessive line pressure; and (3) both material and design affect function, with some designs being safer than others. Cardiac surgeons should base the choice of an arterial perfusion cannula on the best performance and safest design available to avoid cannula-related problems at operation.

Aorta↗
PubMed1985

Antiemetic efficacy of high-dose dexamethasone versus placebo in patients receiving cisplatin-based chemotherapy: a randomized double-blind controlled clinical trial.

The antiemetic effect of short courses of high-dose dexamethasone was compared with that of placebo in 64 patients receiving cisplatin-based cancer chemotherapy, in a double-blind randomized clinical trial. All patients were receiving cisplatin for the first time. Dexamethasone was given intravenously (IV) at a dose of 20 mg, two hours before and 3, 6, 9, and 12 hours after chemotherapy. Patients were crossed over to dexamethasone on the second cycle of chemotherapy if they experienced unacceptable gastrointestinal (GI) toxicity after initial treatment with placebo. Nine of 32 patients receiving dexamethasone and seven of 32 patients receiving placebo did not vomit. The median duration of nausea was significantly shorter (one-half hour) for the dexamethasone-treated group compared with that of placebo (31/2 hours). The number of patients who experienced unacceptable GI toxicity was significantly greater (53%) for the placebo patients than for those treated with dexamethasone (25%). Patients crossing over to dexamethasone after initially receiving placebo had a median duration of nausea of 11/2 hours and 24% did not vomit, results comparable to the first treatment group. We conclude that high-dose dexamethasone is only minimally effective as an antiemetic agent in patients receiving cisplatin-based chemotherapy.

Adult↗
PubMed1984

Oral candidiasis in high-risk patients as the initial manifestation of the acquired immunodeficiency syndrome.

We studied the frequency with which unexplained oral candidiasis led to unequivocal acquired immunodeficiency syndrome (AIDS) in patients at risk. Twenty-two previously healthy adults with unexplained oral candidiasis, of whom the 19 tested had a reversed T4/T8 ratio and 20 had generalized lymphadenopathy, were compared with 20 similar patients with a reversed T4/T8 ratio and generalized lymphadenopathy who did not have oral candidiasis. All were intravenous-drug abusers, homosexual or bisexual men, or both. Thirteen of the 22 patients with oral candidiasis (59 per cent) acquired a major opportunistic infection or Kaposi's sarcoma at a median of three months (range, 1 to 23) as compared with none of 20 patients with generalized lymphadenopathy and immunodeficiency but without candidiasis who were followed for a median of 12 months (range, 5 to 21) (P less than 0.001). AIDS developed in 12 of 15 patients with candidiasis and T4/T8 ratios less than or equal to 0.51, as compared with none of four with ratios equal to or greater than 0.60 (P less than 0.01). We conclude that in patients at high risk for AIDS, the presence of unexplained oral candidiasis predicts the development of serious opportunistic infections more than 50 per cent of the time. Whether the remainder will have AIDS is not yet known.

Acquired Immunodeficiency Syndrome↗
PubMed1984

A sensitive procedure for determination of cathepsin D: activity in alveolar and peritoneal macrophages.

Several new synthetic substrates fulfilling the specificity requirements of cathepsin D were synthesized. One of these D-Phe-Ser(O-CH2-C6H5)-Phe-Phe-Ala-Ala-pAB(pAB = p-aminobenzoate) proved to be highly sensitive and convenient for measuring activity. Enzyme determination was carried out in a two-step reaction. In the first step the enzyme hydrolyzes the Phe-Phe bond of the substrate at pH 3.4. In the second step aminopeptidase M (EC 3.4.11.2) degrades one of the products Phe-Ala-Ala-pAB at pH 7 to 8 with the release of free pAB, which is then determined by a diazotization procedure. Activity can be measured in as little as 1 to 5 micrograms of macrophage protein. The activity of cathepsin D in rat alveolar macrophages was almost ten times higher than in resident peritoneal macrophages, and more than 25 times higher than in blood monocytes. The data indicate that transformation of blood monocytes into macrophages is associated with a much greater increase of cathepsin D activity in alveolar than peritoneal macrophages.

Aminopeptidases↗
PubMed1984

Quantitation of leukocytes in bronchoalveolar lavage samples from rats after intravascular injection of endotoxin.

Although it has been demonstrated in several animal species that neutrophils aggregate in the pulmonary microvasculature after intravenous infusion of chemotactic factors or substances that activate the systemic complement system, studies in rabbits have revealed that affected neutrophils do not migrate out of capillaries into air spaces unless the infusion processes are combined with manipulative procedures involving the airways, such as intubation or instillation of an anesthetic agent. In this study, we report that after intravenous infusion of endotoxin (Escherichia coli) into Sprague-Dawley rats, in the absence of airway manipulation, the absolute number of neutrophils in bronchoalveolar lavage (BAL) samples increased significantly 24 and 48 h after injection. This represented nearly a 24-h delay from the time that maximal numbers of neutrophils were seen in lung tissue and approximately an 18-h delay from the time that maximal numbers appeared in peripheral blood. We also found that after infusion of endotoxin the number of pulmonary alveolar macrophages (PAM) recoverable in BAL samples fell dramatically within 2 h and remained suppressed for at least 12 h. We conclude that: (1) neutrophils are capable of migration into air spaces after aggregation in pulmonary capillaries in the absence of airway manipulative procedures or instillation of chemoattractants into air spaces and (2) endotoxemia affected surface parameters of PAM in vivo that determine recoverability by lavage.

Animals↗
PubMed1984

Detection of endometrial carcinoma and hyperplasia in asymptomatic women.

Occult endometrial carcinoma is a detectable disease using commercially available sampling devices and cytohistologic techniques. A cohort of 2586 asymptomatic women (98% past the age of 45, 78% caucasian) was screened. Of these women, 1567 were screened twice, and 187 were screened three times. The prevalence and incidence rates of endometrial carcinoma, as defined in the present study, including four missed cases, were 6.96 per 1000 and 1.71 per 1000 women years, respectively. The prevalence rate was 7.38 per 1000 for caucasian women and 5.40 per 1000 for women of other races. An epidemiologic evaluation suggested that the onset of menopause past the age of 49 was the only statistically significant risk factor, whereas race, parity, estrogen intake, and obesity, as calculated by the Quetelet index, were not statistically significant. The present study strongly suggests that in asymptomatic women past the age of 50, endometrial hyperplasia does not necessarily precede or accompany the development of endometrial carcinoma. Two distinct mechanisms may be responsible for the onset of endometrial cancer: endometrial hyperplasia occurring in the symptomatic and younger woman; and endometrial adenocarcinoma occurring ab initio in the older patient.

Adenocarcinoma↗